U.S. patent application number 10/925518 was filed with the patent office on 2005-03-03 for device and method for intradermal cell implantation.
Invention is credited to Daddona, Peter, Shaya, Steven.
Application Number | 20050049625 10/925518 |
Document ID | / |
Family ID | 34216163 |
Filed Date | 2005-03-03 |
United States Patent
Application |
20050049625 |
Kind Code |
A1 |
Shaya, Steven ; et
al. |
March 3, 2005 |
Device and method for intradermal cell implantation
Abstract
The present invention relates to a device and method for
implanting hair follicle-inducing cells within the scalp. The hair
follicle cells are generated by the use of tissue culture process
from autologous donor cells. The cells are placed upon a
microprojection array for implantation within the scalp utilizing
predetermined parameters of angle, density and depth.
Inventors: |
Shaya, Steven; (Highlands,
NJ) ; Daddona, Peter; (Menlo Park, CA) |
Correspondence
Address: |
PHILIP S. JOHNSON
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
34216163 |
Appl. No.: |
10/925518 |
Filed: |
August 24, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60498143 |
Aug 26, 2003 |
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Current U.S.
Class: |
606/187 |
Current CPC
Class: |
A61K 9/0021 20130101;
A61P 17/14 20180101; A61M 37/0015 20130101; A61M 2037/003 20130101;
A61M 2037/0038 20130101 |
Class at
Publication: |
606/187 |
International
Class: |
A61B 017/34 |
Claims
What is claimed is:
1. A transdermal delivery system for implanting hair follicles in a
patient comprising a microprojection array having a plurality of
stratum corneum-piercing microprojections and a formulation of
hair-follicle inducing cells deposited on at least one of said
microprojections.
2. The transdermal delivery system of claim 1, wherein said at
least one microprojection has a cavity and said formulation of
hair-follicle inducing cells is deposited within said cavity.
3. The transdermal delivery system of claim 2, wherein said
hair-follicle inducing cells comprise dermal papilla cells cultured
from the group consisting of autologous, allogeneic, and xenogeneic
primary sources.
4. The transdermal delivery system of claim 2, wherein said cavity
has a symmetrical concave configuration.
5. The transdermal delivery system of claim 2, wherein said cavity
further comprises a retention barrier.
6. The transdermal delivery system of claim 5, wherein said
retention barrier is configured to substantially retain said
deposited formulation upon insertion of said microprojection into
tissue and to release said deposited formulation upon withdrawal of
said microprojection from tissue.
7. The transdermal delivery system of claim 6, wherein said cavity
further comprises a sloped leading edge configured to facilitate
release of said deposited formulation upon withdrawal of said
microprojection from tissue.
8. The transdermal delivery system of claim 2, wherein said at
least one microprojection has a broad surface and a narrow
edge.
9. The transdermal delivery system of claim 8, wherein said cavity
is positioned on said broad surface.
10. The transdermal delivery system of claim 9, wherein said cavity
is positioned on said narrow edge.
11. The transdermal delivery system of claim 10, wherein said at
least one microprojection further comprises a pressure conduit
configured to communicate pressure to said cavity to facilitate
dislodging said deposited formulation.
12. The transdermal delivery system of claim 10, wherein said
cavity further comprises a retention pocket that is configured to
substantially retain said deposited formulation upon insertion of
said microprojection into tissue and to release said deposited
formulation upon withdrawal of said microprojection from
tissue.
13. The transdermal delivery system of claim 2, wherein said cavity
is configured to substantially retain said deposited formulation
upon insertion of said microprojection into tissue.
14. The transdermal delivery system of claim 1, wherein said at
least one microprojection has an absolute orientation configured to
produce a desired wound path.
15. The transdermal delivery system of claim 14, wherein said
delivery system further comprises a sheet from which said at least
one microprojection protrudes and said absolute orientation
comprises an angle of said at least one microprojection with
respect to said sheet.
16. The transdermal delivery system of claim 14, wherein said
absolute orientation is configured to result in a desired hair
follicle orientation.
17. The transdermal delivery system of claim 15, wherein said angle
is between about 45 degrees and 90 degrees.
18. The transdermal delivery system of claim 2, wherein said at
least one microprojection has a hydrophobic coating except on said
cavity and wherein said formulation is aqueous.
19. The transdermal delivery system of claim 1, wherein said
formulation is frozen.
20. The transdermal delivery system of claim 1, further comprising
a bioerodible polymer applied to said at least one microprojection
and wherein said formulation is incorporated within said
bioerodible polymer.
21. The transdermal delivery system of claim 1, wherein said
formulation comprises an autologous tissue culture of dermal
papilla cells.
22. The transdermal delivery system of claim 1, wherein said
formulation is selected from the group consisting of allogeneic
cells and xenogeneic cells.
23. A method for treating hair loss in a patient, comprising the
steps of: providing a microprojection array having a plurality of
stratum corneum-piercing microprojections and a formulation of
hair-follicle inducing cells deposited on at least one of said
microprojections; applying said microprojection array to said
patient so that said at least one microprojection pierces the
stratum corneum of said patient; and delivering said formulation of
hair-follicle inducing cells to tissue beneath the stratum
corneum.
24. The method of claim 22, wherein said step of applying said
microprojection array comprises inserting said at least one
microprojection through said stratum corneum so that a substantial
portion of said formulation remains deposited on said
microprojection.
25. The method of claim 23, wherein the step of delivering said
formulation comprises withdrawing said at least one microprojection
so that a substantial portion of said formulation remains in tissue
beneath the stratum corneum.
26. The method of claim 22, further comprising the step of freezing
the formulation on said at least one microprojection and wherein
the step of delivering said formulation comprises allowing said
formulation to thaw after said at least one microprojection pierces
the stratum corneum.
27. The method of claim 22, wherein said microprojection array
further comprises a bioerodible polymer applied to said at least
one microprojection and wherein said formulation is incorporated
within said bioerodible polymer and wherein said step of delivering
said formulation comprises allowing said bioerodible polymer to
dissolve within tissue below the stratum corneum.
28. The method of claim 22, further comprising the step of
selecting an absolute orientation and a relative orientation of
said at least one microprojection to create a desired wound
path.
29. The method of claim 27, further comprising the step of
influencing hair follicle orientation by creating said desired
wound path.
30. A method for growing hair on a patient comprising the step of
transdermally implanting hair follicle-inducing cells with a
microprojection array.
31. A method for forming a hair loss treatment device, comprising
the steps of: providing a microprojection array; and depositing a
formulation of hair follicle-inducing cells on said microprojection
array.
32. The method of claim 30, wherein said step of providing a
microprojection array comprises providing an array having at least
one microprojection with a hydrophobic coating and a
non-hydrophobic cavity and wherein said step of depositing said
formulation comprises applying said formulation to said at least
one microprojection whereby said formulation is retained on said
non-hydrophobic cavity and not retained on said hydrophobic
coating.
33. The method of claim 30, further including the step of freezing
said deposited formulation after said formulation is deposited.
34. The method of claim 30, wherein the said of depositing said
formulation on said at least one microprojection comprises applying
a bioerodible polymer to said at least one microprojection and
incorporating said formulation within said bioerodible polymer.
Description
CROSS REFERENCE TO RELATED APPLICTAIONS
[0001] This application claims the benefit of U.S. Provisional
Application No. 60/498,143, filed Aug. 26, 2003.
FIELD OF THE PRESENT INVENTION
[0002] This invention relates to administering and implanting
viable cells into the tissue of a patient. More particularly, the
invention relates to a cell implantation system for transdermally
delivering viable cells through one or more cellular layers of the
integument surrounding the organism using skin-piercing
microprojections that are preferably adapted to retain the
cells.
BACKGROUND OF THE INVENTION
[0003] The loss of hair (alopecia) due to age and or disease is a
common occurrence. Various methods of correcting this problem have
been tried. Such methods as wigs, toupees, weaves, and even
spray-on-hair have been utilized. These methods attempt to address
the problem by cosmetically hiding or masking the hair loss rather
than halting or reversing the physiological changes that resulted
in the hair loss itself.
[0004] Prior art attempts to correct or reverse hair loss have
utilized pharmaceuticals. A notable example is minoxidil
(Rogaine.RTM.) which is usually applied topically to the scalp.
Finasteride (Propecia.RTM.) is another pharmaceutical intended to
correct hair loss. It is used as an orally delivered systemic
medication. These pharmaceutical approaches have proven variable in
their efficacy of reversing hair loss, and do not work for a
substantial percentage of patients.
[0005] In contrast to pharmaceutical approaches, hair follicle
transplants have provided greater success. Such methods entail the
autologous procedure of the surgical removal of hair follicles or
clusters of hair follicles from regions of the scalp containing
viable follicles and transplanting them to other regions of the
scalp which have sustained hair loss.
[0006] Early procedures required the transplantation of fairly
large clusters of hair cells. This limitation produced a very
artificial look to the resulting hair growth. More advanced
surgical techniques have been developed, allowing transplantation
of smaller and smaller clusters, thus improving the esthetic
quality of the resulting new hair growth.
[0007] Nevertheless, these prior art techniques have certain
limitations. Chiefly, transplantation of existing follicles does
not increase the number of viable follicles, it only relocates
them. If the transplant is initiated with a patient who has already
sustained significant hair loss, there may not be a sufficient
number of follicles to fully restore the entire scalp. Further, the
life span transplanted follicles is uncertain. Moreover, the
physiological basis for the hair loss has not been corrected.
Consequently, the rate at which the follicles will die off may not
have been altered as a result of this transplant. Thus, if a
patient's condition would inherently lead to total baldness, the
transplant procedure may not alter the progression. The
transplanted follicles may follow the normal progression of decay
in the new location.
[0008] Yet another draw back to transplantation procedures is the
high level of skill required for this procedure. They need to be
performed by trained physicians, under sterile conditions and
usually entail multiple sessions of transplantation.
[0009] To overcome these limitations, attempts have been made to
increase the number of viable follicles. For example, a number of
patents have issued which deal with tissue culture growth of hair
progenitor cells and the macro scale surgical placement of these
cells into the skin. In U.S. Pat. No. 4,919,664 to Oliver, it is
disclosed that the placement of cultured dermal papillae cells into
the dermis so that the cells are in contact with epidermal cells
will result in the formation of fully functioning hair follicles.
These cells initiate the differentiation of surrounding cells so
that hair follicles are formed. In the referenced procedure, slits
were made in the skin that were in the range of 1 to 3 millimeters
long and made to a depth greater then the full depth of the
epidermis. The cells were introduced in a volume of from 0.5
microliters to 50 microliters containing 1000 to 1,000,000
cells.
[0010] In another example, WO 02/060039 to Barrows, a procedure is
described in which dermal papillae, a morphological component of
hair follicles, were dissected from donor hair follicles and then
grown in tissue culture media. In this procedure, a
hyaluronate-gelatin matrix was packed inside a needle containing a
0.0035-inch diameter wire. The needle/wire combination was used to
scrape confluent cells from the dermal papilla tissue culture
flasks. The needle/wire and attached cells were placed in culture
media and the cells were allowed to grow for about a week. Then a
small blep was created in the scalp at the location that hair
growth is desired. The blep was created by injecting a solution of
sodium hyaluronate into the scalp. The blep was punctured with a
knife and the wire and the attached cells were then inserted into
the blep. The needle was removed and then later the wire, leaving
the cells positioned within the scalp.
[0011] These references indicate that it is possible to culture
viable hair follicle-inducing cells and seed them in a patient's
scalp. However, these prior art methods require tedious
manipulation and a high level of skill, making them relatively
impractical as a treatment for hair loss.
[0012] Thus, there remains a need for a hair loss treatment that
provides a high rate of true hair restoration, requires less skill
than the traditional hair transplant techniques, increases the
total number of available and viable hair follicles and quickly
treats significant portions of the scalp.
[0013] Accordingly, it is an object of the invention to provide a
method of treating hair loss by transdermally delivering hair
follicles using a microprojection array.
SUMMARY OF THE INVENTION
[0014] In accordance with the above objects and those that will be
mentioned and will become apparent below, the invention comprises a
transdermal delivery system for implanting hair follicles in a
patient with a microprojection array having a plurality of stratum
corneum-piercing microprojections and a formulation of
hair-follicle inducing cells deposited on at least one of the
microprojections.
[0015] Preferably, the microprojections of the array are configured
to retain the formulation. In one embodiment, the cavity is
symmetrical and concave. The cavity can also comprise a retention
barrier, configured to retain the formulation upon insertion and
allow the release of the formulation upon withdrawal of the
microprojection from the tissue. Moreover, the cavity can be
positioned on the broad face of the microprojection or upon the
narrow edge.
[0016] In some embodiments, the microprojection also has a pressure
conduit configured to communicate pressure to the cavity to
facilitate dislodging the formulation.
[0017] In another aspect of the invention, the microprojection has
an absolute orientation configured to produce a desired wound path.
For example, the absolute orientation can be the angle of the
microprojection with respect to the sheet, such as about 45 to 90
degrees. The absolute orientation is configured to result in a
desired hair follicle orientation.
[0018] In one embodiment of the invention, the formulation is
selectively applied to a specific portion of the microprojection.
For example, the microprojection can have a hydrophobic coating
except on the cavity so that the aqueous formulation is retained
only in the cavity.
[0019] In another embodiment, the formulation is frozen on the
microprojection to help retain it during insertion. The formulation
can be allowed to thaw once the microprojection is inserted through
the stratum corneum, to deliver the hair follicle-inducing
cells.
[0020] In yet another embodiment, a bioerodible polymer is applied
to the microprojection and the formulation is incorporated within
the polymer. The array is left in the tissue until the polymer
erodes to deliver the hair follicle-inducing cells.
[0021] Preferably, the devices and methods of the invention are
directed to the implantation of cultured autologous dermal papilla
cells. Alternatively, allogeneic cells and xenogeneic cells can
also be used.
[0022] The method of the invention generally comprises the steps of
providing a microprojection array having a plurality of stratum
corneum-piercing microprojections and a formulation of
hair-follicle inducing cells deposited on at least one of the
microprojections, applying the microprojection array to the patient
so that the microprojection formulation of hair-follicle inducing
cells to tissue beneath the stratum corneum. Preferably, the method
comprises retaining a substantial portion of the formulation on the
microprojection and releasing the formulation upon withdrawal of
the microprojection.
[0023] In an embodiment of the invention, the method also comprises
selecting an absolute orientation and a relative orientation of the
microprojection to create a desired wound path. Preferably, hair
follicle orientation is influenced by creating the desired wound
path.
[0024] The methods of the invention also include growing hair on a
patient by transdermally implanting hair follicle-inducing cells
with a microprojection array.
[0025] Yet another method of the invention is the formation of a
hair loss treatment device by providing a microprojection array and
depositing a formulation of hair follicle-inducing cells on the
microprojection array.
[0026] In one aspect of the invention, at least one microprojection
has a hydrophobic material except for a non-hydrophobic cavity so
that when the formulation is applied to the microprojection, the
formulation is retained only on the non-hydrophobic cavity.
[0027] In another aspect of the invention, the formulation is
frozen on the microprojection array. Alternatively, the formulation
can be included in a bioerodible polymer that is applied to at
least one of the microprojections of the array.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1A is a perspective view of a portion of one embodiment
of the invention, showing a microprojection array having cavities
on some of the microprojections which would retain formulations,
suspensions or coatings of the viable elements;
[0029] FIG. 1B is section view of one microprojection showing one
embodiment of a cavity for retaining a formulation of hair
follicle-inducing cells;
[0030] FIG. 2A is a perspective view of a single microprojection
showing alternate embodiments of two cavities on the
microprojection for containing a suspension of the viable
elements;
[0031] FIG. 2B shows a sectional view of the microprojection shown
in FIG. 2A;
[0032] FIG. 3 is a perspective view of a single microprojection
containing another embodiment of a cavity positioned on an edge of
the microprojection and an optional pressure conduit for enabling
the release of the suspension into the surrounding tissue; and
[0033] FIG. 4 is a perspective view of a single microprojection
similar to the one shown in FIG. 3, but including an additional
retention pocket.
DETAILED DESCRIPTION OF THE INVENTION
[0034] Before describing the present invention in detail, it is to
be understood that this invention is not limited to particularly
exemplified materials, methods or structures as such may, of
course, vary. Thus, although a number of materials and methods
similar or equivalent to those described herein can be used in the
practice of the present invention, the preferred materials and
methods are described herein.
[0035] It is also to be understood that the terminology used herein
is for the purpose of describing particular embodiments of the
invention only and is not intended to be limiting.
[0036] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one
having ordinary skill in the art to which the invention
pertains.
[0037] Further, all publications, patents and patent applications
cited herein, whether supra or infra, are hereby incorporated by
reference in their entirety.
[0038] Finally, as used in this specification and the appended
claims, the singular forms "a, "an" and "the" include plural
referents unless the content clearly dictates otherwise. Thus, for
example, reference to "a microprojection" includes two or more such
microprojections and the like.
Definitions
[0039] The term "microprojections", as used herein, refers to
piercing elements that are adapted to pierce or cut through the
stratum corneum into the underlying epidermis layer, or epidermis
and dermis layers, of the skin of a living animal, particularly a
mammal and more particularly a human. In one embodiment of the
invention, the microprojections have a projection length less than
1000 microns. In a further embodiment, the microprojections have a
projection length of less than 500 microns, more preferably, less
than 250 microns. The microprojections typically have a width and
thickness of about 5 to 50 microns. The microprojections can also
have a width of about 75 to 500 microns. The microprojections can
be formed in different shapes, such as needles, hollow needles,
blades, pins, punches, and combinations thereof. As such, the terms
"microprojections," "microprotrusions," "microblades" and
"microneedles" are used throughout interchangeably.
[0040] The terms "delivery member," "microprojection array" and
"microprojection member", as used herein, generally connote a
plurality of microprojections arranged in an array for piercing the
stratum corneum. The array can be formed by etching or punching a
plurality of microprojections from a thin sheet and folding or
bending the microprojections out of the plane of the sheet to form
a configuration such as that shown in FIG. 1 and described in
Trautman, et al., U.S. Pat. No. 6,083,196, which is hereby
incorporated by reference in its entirety. References to the area
of the sheet or member and reference to some property per area of
the sheet or member, are referring to the area bounded by the outer
circumference or border of the sheet.
[0041] The microprojection array may also be formed in other known
manners, such as by forming one or more strips having
microprojections along an edge of each of the strip(s) as disclosed
in Zuck, U.S. Pat. No. 6,050,988, which is hereby incorporated by
reference in its entirety. Other microprojection members that can
be employed with the present invention include, but are not limited
to, the members disclosed in U.S. Pat. Nos. 6,083,196, 6,050,988,
6,091,975, 5,879,326 and 5,983,136; which are incorporated by
reference herein in their entirety.
[0042] The present invention relies upon the use of tissue culture
techniques to grow dermal papilla cells that are harvested from the
patient. Alternatively, cells obtained from allogeneic sources or
manipulated xenogeneic species could be used. These cells are then
implanted into the scalp of the same patient by the use of a
microprojection array. The cells are implanted so as to be in
contact with the epidermis. This results in the formation of fully
functional hair follicles. A key advantage of this technique is
that it provides an increase in the number of hair follicles
available to the patient, provided there are sufficient viable
follicles still remaining on the scalp that can be harvested and
used to initiate the tissue culture procedures.
[0043] Delivery of the cultured cells is accomplished when the
microprojections pierce the outer integument, such as the stratum
corneum, of the organism and the microprojections deposit the cells
at the appropriate location within or below the integument of the
individual. Specifically, the invention relates to a device and
method that will implant hair-follicle inducing cells at
predetermined locations within the scalp for the purpose of causing
the development of hairs follicles and the subsequent growth of new
hair
[0044] Thus, an aspect of the invention is the use of a small array
of microprojections. The microprojections are designed to hold and
retain hair follicle progenitor cells that have been grown by
tissue culture techniques. This array is loaded with the progenitor
cells on the microprojections and then applied to the scalp. The
microprojections pierce the scalp and deposit the cells. The array
contains microprojections of the appropriate lengths, orientations
and spacing in order to effectuate proper placement of the cells,
in terms of spacing over the surface of the scalp as well, the
depth in the epidermis of the scalp at which the cells are
deposited and the likely orientation of resulting hair
follicles.
[0045] Microprojection arrays offer a number of advantages in the
practice of the invention. Arrays can be created with
microprojections having varying lengths to control penetrations,
with varying densities of microprojections per area to control the
number of hair-follicle inducing cells delivered and with
microprojections having varying angles to control the angle of
entrance of the microprojection into the scalp to dictate the angle
that the resultant hair fiber makes with the scalp. As one having
skill in the art will appreciate, the angle of entrance is a
critical factor in obtaining a natural looking hair pattern.
[0046] Generally, one aspect of the present invention comprises a
microprojection array, a plate or sheet from which a series of
microprojections extend, typically at an angle ranging from 45 to
90 degrees from the plate. Preferably, the length of each
microprojection can physically be in the range of 100 to 600
micrometers. The plate, typically made of metal, preferably
titanium, range in overall area up to 10 cm2. The concentration of
microprojections can range between 10 to 1,000 microprojections per
cm2. Within these physical limitations, all of the above parameters
can be varied in order to provide an implantation regimen to suit
the needs of a particular patient.
[0047] Referring now to FIG. 1A, one embodiment of a
microprojection array 5 is illustrated for use with the present
invention. FIG. 1A shows a portion of microprojection array 5
having a plurality of microprojections 10, which are configured to
pierce or cut a biological surface, such as the stratum corneum. In
this embodiment, the microprojections are formed by etching or
punching a plurality of microprojections 10 from a thin metal sheet
12. As shown, microprojections 10 are bent out of the plane of the
sheet to substantially a 90.degree. angle from sheet 12, partially
forming openings 14. Sheet 12 may be incorporated into a delivery
patch including a backing for sheet 12 (not shown) and may
additionally include adhesive for adhering the patch to the
skin.
[0048] Metals such as stainless steel and titanium are preferred.
Metal microprojection members are disclosed in Trautman et al, U.S.
Pat. No. 6,083,196; Zuck, U.S. Pat. No. 6,050,988; and Daddona et
al., U.S. Pat. No. 6,091,975; the disclosures of which are fully
incorporated herein by reference. Other microprojection members
that can be used with the present invention are formed by etching
silicon using silicon chip etching techniques or by molding plastic
using etched micro-molds. Silicon and plastic microprojection
members are disclosed in Godshall et al., U.S. Pat. No. 5,879,326,
the disclosure of which is fully incorporated herein by
reference.
[0049] Also shown in FIG. 1A are one or more cavities 16, located
on one of the broad surfaces 15a of one or more of microprojections
10. These and other cavities are designed to hold a suspension,
either liquid or frozen of hair-follicle inducing cells. The
hair-follicle inducing cells can also be contained within a
bioerodible polymer, which is deposited within the cavities.
[0050] FIG. 1B is a sectional view of one of the microprojections
10. Cavity 16 is shown in FIGS. 1A and 1B as being circular, but
any number of other shapes are possible, some of which are
disclosed below.
[0051] FIG. 2A illustrates a single microprojection 10.
Microprojection 10, because it must be able to pierce the
biological surface, usually has a flat blade-like shape, with a
broad surface 15a and a narrow edge 15b. Cavity 16 is shown located
along one of the broad surfaces 15a of microprojection 10. Cavity
16 can be a symmetrical concave cavity as shown in FIGS. 1A and 1B.
However, as shown in FIGS. 2A and 2B, cavity 16 can also be
non-symmetrical and adapted to have a retention barrier 18.
[0052] Preferably, cavity 16 is configured so that upon insertion
of microprojection array 5 into the scalp, the formulation
contained in cavity 16 is substantially trapped and/or caught
behind retention barrier 18. This helps prevent the formulation
from being dislodged during insertion. Further, the leading edge 19
of cavity 16 is preferably gently sloped, so that withdrawal of
microprojection array 5 from the scalp allows the formulation to
slide easily out of cavity 16. Thus, the formulation is deposited
within the scalp tissue at the depth that cavity 16 was positioned
after insertion of microprojection array 5.
[0053] The narrow edge 15b may also be the site of a cavity, such
as cavity 24. Cavity 24 can have, but is not limited to, the same
symmetrical configuration as shown in FIGS. 1A and 11B, but could
also have the configuration of cavity 16 as shown in FIGS. 2A and
2B, or the configuration shown in FIGS. 3 and 4.
[0054] FIG. 3 shows cavity 16 located on the leading edge 15c. A
cavity located in this position has the advantage that the
insertion process tends to force the formulation or suspension
located within cavity 16 down into the cavity.
[0055] An optional pressure conduit 17 can be included to allow
exertion of pressure along the conduit to aid in the depositing of
the formulation or suspension within the tissue. Preferably,
pressure conduit 17 can be used to conduct either liquid or gas
pressure to one or more of the microprojections. After the
microprojection array 5 has been inserted into the biological
surface, a brief application of gas or liquid pressure gently urges
the formulation out of cavity 16. Though the pressure conduit is
only shown in FIGS. 3 and 4, it could be included in the
embodiments shown in FIGS. 1A, 1B, 2A or 2B.
[0056] FIG. 4 shows an embodiment similar to that shown in FIG. 3,
but which also includes a retention pocket 20 located in the lower
portion of cavity 16. The addition of the retention pocket further
aids in the retention of the formulation during insertion. The
inclusion of the pressure conduit 17, as described previously aids
in release or deposition of the formulation within the tissue after
the proper insertion of the microprojection array 5.
[0057] As discussed above, the microprojections are designed to
contain cavities or other means of retaining hair follicle inducing
cells. The microprojection array, with the hair follicle inducing
cells disposed within the cavities of the microprojections, is then
inserted into the tissue on the scalp. Though the primary
discussion herein focuses on implanting hair-follicle inducing
cells into the scalp, it should be understood that the device and
methods of the invention can be applied to any area of the body on
which hair is desired to be grown, such as the eyebrows, face or
arms.
[0058] Another aspect of the invention is directed to producing a
desirable orientation of the implanted hair follicles. The delivery
of follicle inducing cells into the scalp leaves a wound for each
entry path. The path of the wounding, or wound path, in the
epidermis during the insertion and withdrawal of the
microprojection array can influence the direction of follicle
development and the orientation that the resulting hair fiber takes
with respect to the implanted tissue. Accordingly, the
microprojection array can be configured to control the orientation
of the entry and withdrawal path of the microprojections.
[0059] Two aspects of the wound path bear upon the appearance of
hair follicle transplantation. The first is the absolute angle that
the path makes with respect to the surface of the tissue. The
second is the relative orientation of the wound path with the
respect to the whole patient. For example, if an implantation is to
be made directly on the top of the head at an absolute orientation
of about 45 degrees with respect to the scalp surface, then the
relative orientation can be chosen to produce a desired pattern.
For example, if the relative orientation is directed towards the
back of the head, then the developing hair shaft generally will be
directed backwards. Correspondingly, if the angle of the wound is
oriented towards the front of the head, then the developing hair
shaft generally will be directed forwards. Thus, the absolute
orientation and the relative orientation angles can be selected to
achieve an aesthetically pleasing pattern of hair growth.
[0060] To control the absolute orientation, microprojections 10 are
positioned at the desired angle relative to the plane of array 5.
The array can then be applied to the scalp in the desired relative
orientation. Preferably, any absolute orientation of
microprojections 10 on array 5 is marked to ensure proper relative
placement. This can be accomplished in any suitable manner. For
example, one edge of the base of the microprojection array could be
notched or in some other manner marked, to indicate the direction
angle of the microprojections.
[0061] In some embodiments, microprojection array 10 is preferably
suspended in a retainer ring as described in detail in Co-Pending
U.S. patent application Ser. No. 09/976,762, filed Oct. 12, 2001,
which is incorporated by reference herein in its entirety. After
placement of the microprojection array 10 in the retainer ring, the
microprojection array 10 is applied to the patient's scalp,
preferably with an impact applicator, such as disclosed in
Co-Pending U.S. patent application Ser. No. 09/976,798, filed Oct.
12, 2001, which is incorporated by reference herein in its
entirety. The microprojection array is attached to the ring by
frangible tabs. When the stored energy within the applicator is
released, a piston is driven onto the microprojection array,
breaking the frangible tabs, releasing the microprojection array
from the mounting ring and driving it into the skin. The ring can
be marked to indicate the direction of angles of the
microprojections mounted therein to facilitate proper relative
orientation upon insertion into the scalp.
[0062] With both the angle of the microprojections and the
orientation properly marked or otherwise indicated, the operator is
able to align the orientation of the microprojection in the desired
direction with respect to the body of the recipient. For example,
it may be desirable to orient the hair follicles perpendicular to a
natural part in the hair, radially around the crown, or
perpendicular to the long axis of the arm.
[0063] In one embodiment, the microprojection array is configured
to be mounted in a handle. Preferably, the array should fit in only
one orientation. Both the handle and the microprojection array can
be adapted so that once assembled, an indicator mark on the handle
allows the operator to apply the microprojection array with the
proper orientation.
[0064] Another aspect of the invention is directed to the
deposition of hair follicle formulations within cavities 16 of
microprojections 10 to effectuate good hair growth. In one
embodiment, all areas of the microprojections 10 except cavities 16
are coated with a hydrophobic material. Then the microprojection
array is then dipped into an evenly dispersed aqueous suspension of
cell clusters. The hydrophobic material repels the aqueous
suspension, allowing only the non-hydrophobic cavities to be
coated. Suitable methods of coating microprojections and apparatus
useful to apply such coatings are disclosed in U.S. patent
application Ser. Nos. 10/045,842, filed Oct. 26, 2001, Ser. No.
10/099,604, filed Mar. 15, 2002, 60/484,142, filed Jun. 30, 2003,
and 60/285,576; the disclosures of which are incorporated by
reference herein.
[0065] In another embodiment, the cell suspensions are deposited
within the cavities of the microprojection array and then frozen.
In this method, each array is used only once. Because of the
relatively small volumes involved, the frozen suspensions, thaw to
a liquid state very quickly once placed within the scalp tissue to
allow deposition of the cell clusters.
[0066] In yet another embodiment, the cell clusters are
incorporated within a bioerodible polymer that is then coated
directly on the microprojections or deposited within one or more
cavities on one or more faces of the microprojections. The
microprojection array is then be inserted into the scalp and left
in place long enough for the polymer to erode and release the cell
clusters into the scalp tissue.
[0067] Without departing from the spirit and scope of this
invention, one of ordinary skill can make various changes and
modifications to the invention to adapt it to various usages and
conditions. As such, these changes and modifications are properly,
equitably, and intended to be, within the full range of equivalence
of the following claims.
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